Methylglyoxal, Cognitive Function and Cerebral Atrophy in Older People

Background. The effects of advanced glycation endproducts on cognition and brain structure are poorly understood. We studied associations of the advanced glycation endproduct precursor methylglyoxal (MGO) with cognitive function and brain volumes in older people. Methods. Nondemented participants in the Tasmanian Study of Cognition and Gait underwent cognitive testing and brain magnetic resonance imaging scans. Brain volumes were obtained by magnetic resonance imaging scan segmentation and statistical parametric mapping procedures. Serum MGO was measured after derivatization to methylquinoxaline by high pressure liquid chromatography and UV detection. Linear regression was used to examine associations of log-transformed MGO with cognitive scores and brain volumes adjusting for potential confounding by age, sex, education, mood, insulin resistance, history of stroke, vascular risk factors, alcohol intake, and psychoactive medication use. Results. There were 378 participants, mean age 72.1 years (SD 7.1), 55% male. Greater MGO was associated with poorer memory (beta = -.12, 95% confidence interval: -0.22, -0.02, p = .02) and executive function, the latter being greater among those with a history of stroke (MGO x stroke beta = .48, 95% confidence interval: 0.17, 0.79, p = .002). Greater MGO was associated with lower grey matter volume (beta = -6.42, 95% confidence interval -11.82, -1.11, p = .02) but not with white matter volume, white matter lesion volume, or hippocampal volume. Conclusions. These results support the investigation of the role of the advanced glycation endproduct precursor methylglyoxal in cognitive decline and neurodegeneration in older people.